EMRA Journal Club: Intravenous Lidocaine for ED Patients with Renal Colic

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Renal colic affects 12% of people worldwide and recurs at a rate of 50%.1 First line therapy for management of pain associated with this condition includes intravenous (IV) non-steroidal anti-inflammatory drugs (NSAIDs), particularly ketorolac.2 While IV lidocaine has shown promise in the management of acute pain, this has not been well studied in the emergency department (ED).3

Two groups in Iran recently studied the use of IV lidocaine for renal colic in the acute care setting.4,5 The research groups were particularly interested in IV lidocaine because IV ketorolac is not available in Iran, and they also note its potential use in patients with allergies or gastrointestinal intolerance to NSAIDs.

Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urology. 2012;12(1):13.

Review by Aadil Vora, MSIV, Nova Southeast University, Ft Lauderdale, FL

Soleimanpour, et al. compared preservative free 2% IV lidocaine to IV morphine in a prospective, double-blind randomized controlled trial (RCT) performed in an ED at a university medical center in Iran. They enrolled 240 patients aged 18 to 65 years, who presented with unilateral flank pain and positive hematuria on urinalysis. They excluded patients who were pregnant, allergic to study medications, or had renal, hepatic, or cardiac disease. All patients first received IV metoclopramide (0.15 mg/kg). Next, 120 patients in one group received a single-dose of lidocaine (1.5 mg/kg) and 120 patients in the second group received a single-dose of morphine (0.1 mg/kg). A Visual Analog Pain Scale (VAS) from zero to 10 was used to establish a baseline pain level at presentation and then 5, 10, 15, and 30 minutes after administration of the pain medication. The authors considered an appropriate response to analgesic as a VAS score of less than three for 30 minutes after the first weight based dose or after the remainder of a prefilled syringe was administered, which initially contained either 200 mg of lidocaine in the first group or 10 mg of morphine in the second group. Results showed that 90% of patients in the lidocaine group and 70% in the morphine group had this response, which was a statistically significant difference. In the lidocaine group, reported side effects included dysarthria (1.7%), perioral numbness (2.5%), and transient dizziness (8.3%).

There are some limitations to this study. First, it is unclear how many of these patients truly had ureteral calculi, since broad inclusion criteria were used and no further confirmatory studies were performed. Additionally, the exact doses of lidocaine and morphine used are unclear. Although a weight-based dose of analgesic was administered initially, there were instances in which additional medication — the remainder of a prefilled syringe — was administered, and it is unclear how this was determined or with what frequency. Finally, they did not clearly state their primary outcome of interest.

Firouzian A, Alipour A, Dezfouli HR, et al. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med. 2016;34(3):443-448.

Review by Nehal Naik, MSIV, Virginia Commonwealth University, Richmond, VA

Firouzian, et al. also performed a single-center double-blind RCT, but, in contrast to the previous trial, they used lidocaine as an adjuvant analgesic. They included patients aged 18 to 50 years with renal colic based on history and physical exam. They excluded patients with a history of asthma, substance abuse, cardiac disease, kidney or liver failure, allergies to lidocaine or morphine, use of analgesics or spasmolytics within 4 hours prior to ED admission, multiple ED admissions for renal colic, pregnancy, or hemodynamic instability. A total of 110 patients were randomized so that 55 received IV morphine (0.1 mg/kg) + IV lidocaine (1.5 mg/kg) while the other 55 received IV morphine 0.1 mg/kg + normal saline (placebo). They measured changes in pain and nausea intensity also using a VAS at time of arrival, 5, 10, 15, 30, 60, and 120 minutes after medication administration. Twenty-one cases were lost to follow-up, including 15 patients in whom nephrolithiasis was not confirmed, leaving only 89 patients in the final analysis.

One of the most significant weaknesses of this study is that, despite a good design, they do not specify a primary outcome or analysis, and performed multiple statistical tests on their pain scores. Overall, their results imply a trend towards improved and quicker control of pain and nausea with IV lidocaine and morphine, though depending how the analyzed their data, these differences were or were not statistically different. In their discussion, they do note that their study was underpowered to detect what they consider a clinically significant pain improvement.

Outcomes Morphine + Lidocaine Morphine alone P Value
Time to pain resolution 87.02 mins 100.12 mins 0.071
Time to nausea resolution 26.6 mins 58.33 mins <0.001

Highlighted Data from Firouzian, et al.

Summary

These two papers study the use IV lidocaine for renal colic in a relatively young, healthy cohort. Both studies suffer from issues with reporting. The first study by Soleimanpour, et al. is particularly vague about some of the methods.

One general research pearl to take away is the importance of setting a single primary outcome before starting a study. This is a simple way, combined with online study registration, to reduce the temptation of performing multiple statistical tests and then only report “statistically significant” differences. Both of these studies are difficult to interpret because they do not specify a primary outcome of interest.

Without the option of IV NSAIDs in Iran, we certainly understand their search for another treatment option. In countries with IV NSAIDs, it is unclear whether there is a benefit to using lidocaine with or instead of NSAIDs and/or opiates. Its potential for use may grow in the US, especially among patients with contraindications to usual analgesia.

The other barrier to IV lidocaine usage for an indication with two longstanding treatment options is that physicians may not be comfortable with its side effects. Neurological side effects including sedation, dizziness, and perioral numbness, typically occur at plasma levels >5 mcg/ml, above the therapeutic window of 2.5-3.5 mcg/ml. Cardiac side effects including decreased contractility, prolonged PR and QRS intervals, atrioventricular disassociation, or possible cardiac arrest typically occur after a patient has neurological symptoms and a plasma concentration over 10 mcg/ml. Despite these risks, previous authors have expressed comfort with IV lidocaine’s safety profile in analgesia.3

Both authors present IV lidocaine as an option to reduce opioid use, though this potential seems minimal. Since lidocaine has been proposed only to replace one dose of morphine in the ED at most, there is little hope that this will have any significant impact on the current state of opioid use.

Both papers introduce early and intriguing data on the use of IV lidocaine in the ED. As is usually the case, more research is needed — fortunately, more is on the way with three RCTs registered on ClinicalTrials.gov investigating the use of IV lidocaine for renal colic.

References

  1. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350:684–693.
  2. Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev. 2005;2:CD004137.
  3. Eipe N, Gupta S, Penning J. Intravenous lidocaine for acute pain: An evidence-based clinical update. BJA Education. 2016;16(9):292-298.
  4. Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urology. 2012;12(1):13.
  5. Firouzian A, Alipour A, Dezfouli HR, et al. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med. 2016;34(3):443-448.
Joshua Mirkin, MD

Joshua Mirkin, MD

Journal Club Column Reviewer, Albert Einstein Medical Center, Philadelphia, PA, @joshmirkin
Olga Kovalerchik, MD

Olga Kovalerchik, MD

EMRA Research Committee Chair, Journal Club Editor, Yale University, New Haven, CT
Olga Kovalerchik, MD

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